Racial Differences in Benefits of ACE Inhibitors in Hypertension: ALLHAT Substudy - Racial Differences in Benefits of ACE Inhibitors in Hypertension: ALLHAT Substudy


The goal of the study was to evaluate differences between blacks and non-blacks in responses to angiotensin-converting enzyme (ACE) inhibitor treatment.

Study Design

Study Design:

Patients Enrolled: 33,357
Mean Follow Up: Mean 4.9 years
Mean Patient Age: 55+ (average 67 years)
Female: 47

Patient Populations:

Men and women age >=55 years with SBP >=140mmHg and/or DBP >=90 mmHg or took medication for hypertension and had at least one additional risk factor for CHD (prior MI or stroke, LVH by ECG or echocardiogram, type 2 diabetes, current smoking, low HDL).


History of hospitalized or treated symptomatic heart failure and/or known LV ejection fraction <35%.

Primary Endpoints:

Fatal coronary heart disease and nonfatal MI.

Secondary Endpoints:

All-cause mortality, stroke, and major cardiovascular disease events (CHF, coronary revascularization, angina, and peripheral artery disease).

Drug/Procedures Used:

Patients in the ALLHAT trial were randomized to chlorthalidone (12.5-25 mg/day; n=15,255), doxazosin (2-8 mg/day, n=9,067), amlodipine (2.5-10 mg/day, n=9,048), or lisinopril (10-40 mg/day, n=9,054) in a ratio of 1.7:1:1:1. Therapeutic goal was SBP <140 mmHg and DBP <90 mmHg. If BP goal was not met on maximal dosage, an open-label Step 2 or3 agent could be added (atenolol, reserpine, or clonidine). Patients were seen every 3 months during first year and every 4 months thereafter.

For the present substudy analysis, patients were categorized as blacks or non-blacks, which included Caucasian, Hispanic and all other races. The treatment effect between the chlorthalidone and lisinopril groups was evaluated.

Principal Findings:

Systolic blood pressure (SBP) at 5 year follow-up was in black subjects was 135.0 mm Hg in the chlorthalidone group and 139.1 mm Hg in the lisinopril, a 4 mm Hg difference between treatment arms. In non-black subjects, SBPs were 133.3 and 133.8 mm Hg, respectively, a much smaller and nonsignificant difference.

In the subgroup of black subjects, there was a non-significantly higher primary event rate of fatal CHD or nonfatal MI in the lisinopril arm vs the chlorthalidone arm (hazard ratio [HR] 1.10, 95% CI 0.94-1.28), with opposite results in the non-black population (HR 0.94, 95% CI 0.85-1.05). Similar directionality of higher event rates in the lisinopril arm among black subjects was reported for the endpoints of all-cause mortality (HR 1.06, 95% CI 1.02-1.30), combined CHD (HR 1.15, 95% CI 1.09-1.30) and cardiovascular disease events (HR 1.19, 95% CI 1.17-1.68).

In non-black subjects, the hazard ratios were as follow: all-cause mortality (HR 0.97, 95% CI 0.89-1.06), combined CHD (HR 1.01, 95% CI 0.93-1.09) and cardiovascular disease events (HR 1.06, 95% CI 1.00-1.13).


Among hypertenisve black patients, initial treatment with the ACE inhibitor lisinopril was associated with a higher blood pressure and a trend toward higher cardiovascular event rates compared with initial treatment with the diuretic chlorthalidone. Prior studies have suggested possbile differences between blacks and non-blacks in blood pressure response to ACE inhibitor treatment. The presenter stated that given these findings, in his opinion diuretics, not ACE inhibitors, should be the first line of hypertensive therapy in black patients.


Presented by Dr. Curt D. Furberg at the American College of Cardiology Scientific Sessions, March 2004.

Keywords: Stroke, Follow-Up Studies, Chlorthalidone, Reserpine, Diabetes Mellitus, Type 2, Diuretics, Clonidine, Risk Factors, Doxazosin, Electrocardiography, Hispanic Americans, Smoking, Lisinopril, Amlodipine, Hypertension

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